Intravascular stents have been permanently implanted in coronary or peripheral vessels to prevent restenosis. See, e.g. U.S. Pat. Nos. 5,800,507; 5,059,166 and 5,840,009. Trauma or injury to the artery caused by angioplasty procedures, implantation of stents, atherectomy or laser treatment of the artery, result in restenosis, i.e., the closure or renarrowing of the artery. Restenosis, a natural healing reaction to the injury of the arterial wall, begins with the clotting of blood at the site of the injury, followed by intimal hyperplasia, i.e. the rapid growth of the injured arterial tissue through the openings in the stent, and the migration and proliferation of medial smooth muscle cells, until the artery is again stenotic or occluded.
However, such stents are not always effective in preventing restenosis and can cause undesirable local thrombosis. A variety of solutions have been proposed to minimize these undesirable effects, such as coating the stents with a biocompatible or an anti-thrombotic surface, wherein the stent-surface is seeded with endothelial cells or fibrin, or using stents as drug delivery devices. See for example, U. S. Pat. Nos. 5,800,507;5,059,166; WO 91/12779 and WO 90/13332.
Implanted stents, in conjunction with endovascular irradiation, are believed to prevent restenosis by alleviating neointimal hyperplasia. The beta-particle emitter, phosphorus-32 (.sup.32 P) radioisotope, has been used as a permanent medical implant. Fischell et al. describe stents formed from radioactive materials, wherein a radioisotope is incorporated into the stent by physical methods, such as coating, plating, implanting on the exterior surface of the stent; inserting inside the stent; and alloying into the metal from which the stent is made. Alternatively, a beam of an ionized radioisotope is directed on the surface of the stent. See U.S. Pat. Nos. 5,059,166, 5,176,617, 5,722,984, and 5,840,009. Typically, an ion-implantation method requires irradiating sublimed red phosphorous (to avoid contamination) for about ten days to achieve a sufficient concentration of phosphorous-32 (.sup.32 P) to obtain radioactivity of 4 to 13 .mu.Ci per stent. However, this method is expensive, requires sophisticated equipment, and the transfer of the radioactive source from the nuclear reactor to the ion-implanter to the medical site adversely affect the short half-life of phosphorous-32 (.sup.32 P) (14.3 days). Additionally, ion-implantation damages the surface of the stent, the interstitially implanted phosphorous-32 (.sup.32 P) diffuses rapidly and is relatively unstable compared to chemically bound phosphorous-32 (.sup.32 P). Moreover, ion-implantation requires beam and/or substrate scanning to achieve uniformity, which is difficult to obtain on a radial open-mesh stent. Thus conventional methods result in lower quality, non-uniform radioactive stents.
Strathearn, et al. describe a process for diffusing chemically bound radioactive ions below the surface of the substrate, wherein diffusion is accomplished by heating the substrate between 300.degree. to 600.degree. C. (U.S. Pat. No. 5,851,315). However, current techniques do not provide for radioactive stents with a radioisotope concentrated at the point of maximum tissue penetration, wherein the radioisotope, such as phosphorus-32 (.sup.32 P), is chemically bound to and is uniformly confined to the surface without affecting the metallurgical properties, such as ductility and malleability, of the stent. Thus, there is a need for improved and cost-effective radioactive stents, wherein the radioisotope is uniformly distributed over the surface and is concentrated at the point of maximum tissue penetration.